Ad-PSMA转染树突状细胞与细胞因子诱导的杀伤细胞共培养的体内抗前列腺癌作用  

Antitumor Effects of Ad-PSMA-Pulsed Dendritic Cells Cocultured with Autologous Cytokine-Induced Killer Cells on Prostate Cancer in Vivo

作　　者：王可兵[1] 高新[2] 庞俊[2] 刘小彭[2] 方建明[1] 杨伟锋[1] 夏宏辉[1] 

机构地区：[1]广东医学院附属南山医院泌尿外科,广东深圳518052 [2]中山大学附属第三医院泌尿外科,广东广州510630

出　　处：《武汉大学学报（医学版）》2013年第6期814-817,共4页Medical Journal of Wuhan University

基　　金：国家自然科学基金资助项目(编号:30471730)

摘　　要：目的:探讨前列腺特异性膜抗原基因复制缺陷型腺病毒(Ad-PSMA)转染的树突状细胞(DC)与细胞因子诱导的杀伤细胞(CIK)共培养后回输体内能否抑制前列腺癌生长。方法:24只免疫缺陷雄性小鼠皮下接种LNcaP细胞构建前列腺癌(PCa)模型。将荷瘤小鼠分成4组,分别回输生理盐水(NS)、CIK、Ad-DC-CIKs以及Ad-PSMA-DC-CIKs,6周后处死小鼠,记录肿瘤重量并行病理学检查和TUNEL凋亡分析。结果:治疗后肿瘤重量在CIK和Ad-DC-CIKs组无显著性差异(P>0.05),其他组间均有显著性差异(P<0.01)。病理学和TUNEL凋亡分析显示NS组PCa腺体结构完整,CIK和Ad-DC-CIKs组移植瘤癌巢部分破坏,而Ad-PSMA-DC-CIKs组癌巢完全破坏,肿瘤细胞片状坏死,凋亡显著。结论:Ad-PSMA负载的DC与CIK共培养回输体内诱导前列腺癌细胞凋亡和坏死,显著抑制肿瘤生长,该研究为PCa尤其是激素难治性PCa提供了一种有效的免疫治疗手段。Objective： To test whether immunotherapy with dendritic cells （DC） transduced by adenovi- ral vector carrying prostate specific membrane antigen （Ad-PSMA） and coeultured with cytokine- induced killer cells （CIK） is capable of inhibiting prostate cancer （PCa） in vivo. Methods： Twen- ty-four inbred male severe combined immunodeficiency mice were used to generate animal PCa model by subcutaneously implanting LNcaP cells. When the tumor reached 4.5-5.5 mm in diame- ter, mice were randomly divided into four equal groups and treated with normal saline （NS）, CIK, Ad-DC-CIKs, or Ad-PSMA-DC-CIKs on day 7 of the cocultivation respectively. Every mouse was intravenously injected every other day for five times. Six weeks after the first injec- tion, mice were sacrificed and tumor weight were recorded. Subcutaneous tumors were checkedby HE staining and TUNEL assay. Results： After treatment, there was no significant difference in tumor weights between CIK and Ad-DC-CIKs group, but among other groups. By histopatho- logical examination, the glandular structures of PCa were partially destroyed in CIK and Ad-DC- CIKs groups. However, cancer nests were completely destroyed in Ad-PSMA-DC-CIKs group. The apoptosis cells were significantly increased in Ad-PSMA-DC-CIKs group than in CIK group. Conclusion： Ad-PSMA-pulsed DC cocultured with autologous CIK induced necrosis and apoptosis of PCa cells and significantly inhibited tumor growth in vivo. This provides a potential immuno- therapy strategy for hormone-refractory PCa.

关 键 词：前列腺特异性膜抗原 腺病毒 树突状细胞 细胞因子诱导的杀伤细胞 前列腺癌 

分 类 号：R737.25[医药卫生—肿瘤]